Departamento de Química, Universidad de La Rioja, Centro de Investigación en Sintesis Química, Grupo de Sintesis Química de La Rioja, UA-CSIC, 26006 Logroño, Spain.
J Org Chem. 2009 Dec 18;74(24):9305-13. doi: 10.1021/jo901988w.
The synthesis and the conformational analysis in aqueous solution of a peptide and a glycopeptide containing the sequence threonine-alanine-alanine (Thr-Ala-Ala) are reported. Furthermore, the threonine residue has been replaced by the quaternary amino acid alpha-methylserine (MeSer) and their corresponding non-natural peptide and glycopeptide are also studied. The conformational analysis in aqueous solution combines NOEs and coupling constants data with Molecular Dynamics (MD) simulations with time-averaged restraints. The study reveals that the beta-O-glycosylation produces a remarkable and completely different effect on the backbone of the peptide derived from Thr and MeSer. In the former, the beta-O-glycosylation is responsible for the experimentally observed shift from extended conformations (peptide) to folded ones (glycopeptide). In contrast, the beta-O-glycosylation of the MeSer-containing peptide, which clearly shows two main conformations in aqueous solution [extended ones (70%) and beta-turn (30%)], causes a high degree of flexibility for the backbone.
报告了含有苏氨酸-丙氨酸-丙氨酸（Thr-Ala-Ala）序列的肽和糖肽的合成和在水溶液中的构象分析。此外，还研究了用季铵氨基酸α-甲基丝氨酸（MeSer）取代苏氨酸残基的相应非天然肽和糖肽。在水溶液中的构象分析结合了 NOE 和偶联常数数据与分子动力学（MD）模拟的时间平均约束。研究表明，β-O-糖基化对来源于 Thr 和 MeSer 的肽的骨架产生显著且完全不同的影响。在前者中，β-O-糖基化负责实验观察到的从伸展构象（肽）到折叠构象（糖肽）的转变。相比之下，含有 MeSer 的肽的β-O-糖基化，其在水溶液中明显显示出两种主要构象[伸展构象（70%）和β-转角（30%）]，导致骨架具有高度的灵活性。
